Vendrell Joan, Chacón Matilde R
Research Unit, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili , Tarragona , Spain.
Front Immunol. 2013 Dec 30;4:488. doi: 10.3389/fimmu.2013.00488.
Obesity and type 2 diabetes (T2D) are associated with chronic low-grade inflammation. Mounting evidence suggests the involvement of an inflammatory switch in adipose tissue, both in mature adipocytes and immune-competent cells from the stromal vascular compartment, in the progression of obesity and insulin resistance. Several inflammatory cytokines secreted by obese adipose tissue, including TNFα and IL-6 have been described as hallmark molecules involved in this process, impairing insulin signaling in insulin-responsive organs. An increasing number of new molecules affecting the local and systemic inflammatory imbalance in obesity and T2D have been identified. In this complex condition, some molecules may exhibit opposing actions, depending on the cell type and on systemic or local influences. Tumor necrosis factor weak inducer of apoptosis (TWEAK), a cytokine of the tumor necrosis (TNF) superfamily, is gaining attention as an important player in chronic inflammatory diseases. TWEAK can exist as a full-length membrane-associated (mTWEAK) form and as a soluble (sTWEAK) form and, by acting through its cognate receptor Fn14, can control many cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. Notably, sTWEAK has been proposed as a biomarker of cardiovascular diseases. Here, we will review the recent findings relating to TWEAK and its receptor within the context of obesity and the associated disorder T2D.
肥胖与2型糖尿病（T2D）与慢性低度炎症相关。越来越多的证据表明，在肥胖和胰岛素抵抗的进展过程中，脂肪组织中的炎症开关发挥了作用，无论是在成熟脂肪细胞还是基质血管成分中的免疫活性细胞中。肥胖脂肪组织分泌的几种炎性细胞因子，包括肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6），已被描述为参与这一过程的标志性分子，它们会损害胰岛素反应器官中的胰岛素信号传导。越来越多影响肥胖和T2D中局部和全身炎症失衡的新分子被发现。在这种复杂的情况下，一些分子可能会根据细胞类型以及全身或局部影响而表现出相反的作用。肿瘤坏死因子凋亡弱诱导剂（TWEAK）是肿瘤坏死（TNF）超家族的一种细胞因子，作为慢性炎症性疾病的一个重要参与者正受到关注。TWEAK可以以全长膜相关（mTWEAK）形式和可溶性（sTWEAK）形式存在，并且通过作用于其同源受体Fn14，可以控制许多细胞活动，包括增殖、迁移、分化、凋亡、血管生成和炎症。值得注意的是，sTWEAK已被提议作为心血管疾病的生物标志物。在此，我们将在肥胖及相关疾病T2D的背景下，综述与TWEAK及其受体相关的最新研究发现。
